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Open Access Highly Accessed Research article

Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

Thewarach Laha1, Porntip Pinlaor2, Jason Mulvenna3, Banchob Sripa2, Manop Sripa2, Michael J Smout3, Robin B Gasser4, Paul J Brindley5 and Alex Loukas3*

Author Affiliations

1 Department of Parasitology, Khon Kaen University, Khon Kaen, Thailand

2 Department of Pathology, Khon Kaen University, Khon Kaen, Thailand

3 Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia

4 Department of Veterinary Science, University of Melbourne, Melbourne, Australia

5 Department of Tropical Medicine, Tulane University Health Sciences Center, New Orleans, USA

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BMC Genomics 2007, 8:189  doi:10.1186/1471-2164-8-189

Published: 22 June 2007

Abstract

Background

Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome.

Results

Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA.

Conclusion

This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes.